Richard Nettles presented preliminary monotherapy data on BMS-663068, a potential first-in-class oral HIV attachment inhibitor. The drug works by binding to the viral envelope glycoprotein gp120 and interfering with the attachment of HIV to the cellular CD4 receptor.

In single and multiple dose studies with healthy study participants, BMS-663068 was well-tolerated and had a pharmacokinetic profile supportive of once- or twice-daily dosing without ritonavir (RTV, Norvir) boosting.

If proven effective and safe in upcoming phase 2 and 3 studies, this drug will be a welcome addition to the HIV entry inhibitor medication class. Maraviroc (MVC, Selzentry, Celsentri), although it was approved back in 2007 in the U.S., it remains the only approved drug in that family at the present. It is taken twice a day and it requires an expensive tropism test to determine which patients can respond to the drug. The cost and slow turnaround time for the tropism test results have been barriers to maraviroc’s access in federally funded clinics around the U.S.

In addition, when maraviroc was approved for treatment-naive HIV-infected patients, it was in combination with zidovudine/lamivudine (AZT/3TC, Combivir), since the approval studies were performed with that fixed-dose combination drug rather than tenofovir/emtricitabine (TDF/FTC, Truvada).

Taken together, all of these factors — twice-a-day dosing, tropism test requirement and lack of long-term data in combination with tenofovir/emtricitabine — help explain why maraviroc is only recommended as a third-tier “acceptable” regimen instead of a first-tier “preferred” regimen in the U.S. Department of Health and Human Services’ HIV treatment guidelines. As a result, the need for a once-a-day entry inhibitor that can be used in combination with tenofovir/emtricitabine, and that does not require an additional (non-phenotype) test to predict response, has motivated other companies to develop entry inhibitors that may get included in the more popularly used “preferred” regimen category.

On the tropism test issue, Nettles showed that a phenotype test that measures IC50 would be a good predictor of BMS-663068 response in patients. The test could be included in current phenotype tests that are readily available in clinics.

Of course, many questions about BMS-663068 remain unanswered. For instance, interaction data with other HIV antiretrovirals has yet to be presented. Meanwhile, studies combining this compound with optimized background therapy that includes at least two other HIV medications (tenofovir/emtricitabine being the most commonly used) will be performed in the near future.

Nonetheless, although it remains relatively early in its development, BMS-663068 shows some promise as a potential first-in-class oral HIV attachment inhibitor.